Int J Biol Sci 2014; 10(3):309-320. doi:10.7150/ijbs.7475
CARP, a Myostatin-downregulated Gene in CFM Cells, Is a Novel Essential Positive Regulator of Myogenesis
1. Institute of Neurology, Guangdong Medical College, Zhanjiang 524001, China;
2. Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China;
3. Department of General Surgery, First Affiliated Hospital of Harbin Medical University, Harbin 150001, China;
4. National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
* These authors contributed equally to this work.
Myostatin, a member of the TGF-β superfamily, has been shown to act as a negative regulator of myogenesis. Although its role in myogenesis has been clearly documented through genetic analysis, few gene cascades that respond to myostatin signaling and regulate myogenesis have been characterized, especially in avian species. In a previous study, we screened for such genes in chicken fetal myoblasts (CFMs) using the differential display PCR method and found that cardiac ankyrin repeat protein (CARP) was downregulated by myostatin and specifically expressed in chicken skeletal muscle. However, little is known about the potential functions of CARP in chicken skeletal myogenesis. In this study, the expression patterns of chicken CARP and the possible function of this gene in skeletal muscle growth were characterized. Our data showed that CARP was predominantly expressed in postnatal skeletal muscle, and its expression increased during myogenic differentiation in CFM cells. When CARP was overexpressed, CFM cell growth was enhanced by accelerating the cell cycle at the G1 to S phase transition and increasing cyclin D1 expression. CARP knockdown had the opposite effect: while myoblasts underwent differentiation, knockdown of CARP expression induced extensive cell death, suppressed the formation of myotubes, and markedly decreased the expression of differentiation-related genes such as myosin heavy chain (MHC), myoD, and caveolin-3. Our findings indicate that CARP may play a key role in the myostatin signaling cascade that governs chicken skeletal myogenesis through promoting proliferation and avoiding apoptosis during CFM cell differentiation.
Keywords: CARP, myostatin, chicken fetal myoblast, skeletal muscle, development.
Ma G, Wang H, Gu X, Li W, Zhang X, Cui L, Li Y, Zhang Y, Zhao B, Li K. CARP, a Myostatin-downregulated Gene in CFM Cells, Is a Novel Essential Positive Regulator of Myogenesis. Int J Biol Sci 2014; 10(3):309-320. doi:10.7150/ijbs.7475. Available from http://www.ijbs.com/v10p0309.htm